Urinary incontinence (UI) with urinary urgency and/or frequency and Overactive Bladder (OAB) are common problems affecting one in five people in the United States. The total affected population is difficult to quantify as it is often under-reported. NIH and the Simon Foundation estimates suggest that between 17 and 33 million people in the United States are affected. NAFC (National Association for Continence) estimates on the basis of multiple studies and expert opinion that 25 million adult Americans experience transient or chronic urinary incontinence.
Bladder weakness affects 25% of reproductive age women, 50% of post-menopausal women, and 50%-75% of women in nursing homes. In men, 60% over the age of 60 experience benign prostate enlargement and associated OAB symptoms. Bladder problems remain under-diagnosed and under-reported.
Bladder control problems can occur for many reasons. Temporary bladder control problems may be caused by, for example, urinary tract infections, vaginal infections or irritation, constipation, and certain medicines. Longer lasting or chronic incontinence can be caused by, for example, both overactive and weak bladder muscles, obstruction from an enlarged prostate, damage to nerves that control the bladder from diseases such as multiple sclerosis or Parkinson's disease, or diseases such as arthritis that can make walking painful and slow.
The basic types of bladder control problems include urinary urgency, urinary frequency, incontinence (bladder accidents with involuntary loss of urine) and nocturia (having to get out of bed at night for the toilet). Overactive bladder in many cases refer to both urinary frequency and urgency.
There are multiple types of urinary incontinence, which include, for example, stress incontinence, urge incontinence, overflow incontinence, and functional incontinence. Stress incontinence happens when urine leaks during exercise, coughing, sneezing, laughing, lifting heavy objects, or other body movements that put pressure on the bladder. It is the most common type of bladder control problem in younger and middle-age women. In some cases, it is related to the effects of childbirth. It may also begin around the time of menopause.
In some embodiments, urge incontinence can happen when a person cannot hold his or her urine long enough to get to the toilet in time. Healthy people can have urge incontinence, but it is often found in people who have diabetes, stroke, Alzheimer's disease, Parkinson's disease, or multiple sclerosis. It is also sometimes an early sign of bladder cancer.
In some embodiments, overflow incontinence can happen when small amounts of urine leak from a bladder that is always full. A man can have trouble emptying his bladder if an enlarged prostate is blocking the urethra. Diabetes and spinal cord injury can also cause this type of incontinence. Functional incontinence can happen in many older people who have normal bladder control. They have a hard time getting to the toilet in time because of arthritis or other disorders that make moving quickly difficult.
Medical treatments for bladder control problems, UI, and OAB can include physical and behavioral therapies, such as Kegel's pelvic floor exercises and bladder retraining; drug medications; devices such as catheters; and surgery may also be an option for some sufferers. Current drug therapies include anticholinergics (with antispasmodic effects, e.g., oxybutinin), smooth muscle relaxants (antispasmodics), tricyclic antidepressants (e.g., imipramine), alpha-adrenergic antagonists, alpha-adrenergic agonists (e.g., phenylpropanolamine), prostaglandin synthesis inhibitors, calcium channel blockers and others (Sullivan and Abrams, Eur. Urol., 36 Suppl 1:89-95 (1999); Andersson, Baillieres Best Pract. Res. Clin. Obstet. Gynaecol., 14(2): 291-313 (2000); Owens and Karram, Drug Saf., 19(2): 123-39 (1998); Wada et al., Arch. Int. Pharmacodyn Ther., 330(1): 76-89 (1995)). Unfortunately, most drug treatments are associated with unpleasant side effects, and this affects on patient compliance (Sullivan and Abrams, Eur. Urol., 36 Suppl 1: 89-95 (1999); Andersson, Baillieres Best Pract. Res. Clin. Obstet. Gynaecol., 14(2): 291-313 (2000); Owens and Karram, Drug Saf., 19(2):123-39 (1998); Wada et al., Arch. Int. Pharmacodyn Ther., 330(1): 76-89 (1995))2-5.
Acetylcholine is the primary excitatory neurotransmitter involved in bladder emptying. Certain drugs commonly prescribed for urinary incontinence, such as oxybutynin hydrochloride, inhibit the muscarinic action of acetylcholine on smooth muscle, producing a direct antispasmodic action. These drugs relax the detrusor muscle. Wada Y. et al., Arch. Int. Pharmacodyn. Ther., 330(1):76-89 (1995); Tapp A. J. S. et al., Brit. J. Obstetrics Gynecology, 97: 521-6 (1990). These medications also produce unwanted anticholinergic effects, such as dry mouth, blurred vision and constipation. Pathak A S, Aboseif S R. Overactive Bladder: Drug therapy versus nerve stimulation. Nat Clin Pract Urol, 2(7): 310-311, 2005; Wein (2001). Natural therapies have also been investigated for this condition (Steels et al., Aust. Continence J., 7(2): 34-37 (2001); Karantanis et al., Aust. Continence J., 6(4): 6-7 (2000); Arya et al., Obstetrics and Gynecology, 96(1): 85-89 (2000); Bryant et al., Aust. Continence J., 6(4): 8 (2000)). In Ayurveda, Crateva nurvala is a drug highly regarded for its use in the management of uropathies (Nadkarni, Indian Materia Medica. Bombay Popular Prakashan). Western traditional treatments recommend the use of Equisetum arvense (British Herbal Pharmacopeia. Publ: British Herbal Medicine Association 1983). Chinese medicine values Lindera for its various properties (Bensky D and Gamble A, 1993. Chinese Herbal Materia Medica, Revised Edition. England Press, Seattle, Wash., USA.)
Isolated clinical studies conducted using herb-based natural therapies for urinary incontinence include Crateva nurvala herb, acupuncture and dietary intervention such as modification of dietary intake. Deshpande et al., Indian J. Med. Res. 76(supp): 46-53, 1982; Karantanis et al., Aust. Continence J., 6(4): 6-7, 2000; Arya et al., Obstetrics and Gynecology, 96(1): 87-89, 2000; Bryant et al., Aust. Continence J., 6(4): 8, 2000.
In some embodiments, overactive bladder (OAB) is a condition that can be characterized by the sudden need to urinate. If that need results in the unintentional leakage of urine, the condition is called urge incontinence (“OAB wet”). Thus, urge incontinence falls within the general definition of OAB in some embodiments. In some embodiments, OAB can result from the sudden, involuntary contraction of the muscle in the wall of the urinary bladder. Approximately one-third of people with OAB also experience urge incontinence (“OAB wet”), while approximately two-thirds have OAB without urge incontinence (“OAB dry”). According to the National Overactive Bladder Evaluation, OAB affects 16.5% of the population, with 16.9% of women and 16.0% of men affected. Stewart et al., World J. Urol. 20: 327-336, (2003). OAB, like urinary incontinence, is treated primarily with anticholinergic drugs (e.g., oxybutinin). These inhibit the neurotransmitter acetylcholine from attaching to the bladder muscle, and thereby reduce the frequency and intensity of contractions of the bladder. Unfortunately, adverse side effects of these drugs include dry mouth, dry eyes, constipation, and headache. Anderson, Urology, 3A: 32-41 (2004); Cruz, Urology. 3A: 65-73 (2004); Appell et al., Mayo Clinical Proc., 78:696-702. (2003).
There are currently no medications that specifically target incontinence or OAB symptoms without having side effects elsewhere in the body. Herbal approaches to bladder problems that improve the tone and tissue strength of the bladder and surrounding area are proving to be effective for bladder control problems. (See, U.S. Pat. No. 7,378,115; and Schauss A G, Spiller G, Chaves S, Gawlicka A, 2006. Reducing the symptoms of overactive bladder and urinary incontinence: results of a two-month, double-blind, placebo-controlled clinical trial. Poster presentation FASEB, San Francisco, April, 2006.) The timeframe for these herbal preparations to produce effective improvements in bladder control is two to three months. In may instances, the length of time before effective results are experienced can result in distress and discomfort for the patient, as well as an expected reduction in patient compliance with the treatment. Herbal treatments that produce results within a shorter timeframe are warranted.
Thus, a need exists for the identification of new herb-containing compositions that can provide effective prevention or treatment of urinary incontinence and overactive bladder.